The focus of this research is age-related hearing loss (presbyacusis). Currently, 28 million Americans have impaired hearing and approximately 75% of these persons are over the age of 55. The prevalence of presbyacusis will increase substantially by the year 2020. To meet the challenges of this most prevalent handicapping condition, new information, diagnostic methods, rehabilitation procedures, and cost-effective access to new technologies will be of great importance. Prevention of presbyacusis and a reduction in its prevalence are even greater challenges. The overall objective of our research program is to improve diagnostic, rehabilitative, and preventive measures. Toward this objective, four research projects are proposed. Project 1 addresses basic questions related to the understanding of speech and benefit of hearing aids in realistic listening environments by older adults. Project 2 is a neuroimaging study that examines the structure and function of neural elements that are hypothesized to contribute to age-related declines in speech recognition in older adults. Project 3 identifies specific alleles associated with age- related hearing loss in carefully selected candidate genes through genotype-phenotype association studies and initiates studies aimed at characterizing the histopathological changes associated with age-related hearing loss in general, and when known, with specific mutations. Project 4 determines the potential role of human hematopoietic stem cells in the maintenance of non-sensory cells in the inner ear and characterizes the effects of aging and cochlear injury on this process. In addition, two cores provide administrative, technical, and scientific support including recruitment of human subjects; collection and storage of human tissue; and collection, storage, and analysis of data. The proposed program of research on presbyacusis in the long term will influence health care of the presbyacusic patient, will affect care of hearing-impaired persons in general, and will have significant impact on theoretical and applied issues in the science of audition.